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      Maternal parity and its effect on adipose tissue deposition and endocrine sensitivity in the postnatal sheep

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          Abstract

          Maternal parity influences size at birth, postnatal growth and body composition with firstborn infants being more likely to be smaller with increased fat mass, suggesting that adiposity is set in early life. The precise effect of parity on fat mass and its endocrine sensitivity remains unclear and was, therefore, investigated in the present study. We utilised an established sheep model in which perirenal–abdominal fat mass (the major fat depot in the neonatal sheep) increases ∼10-fold over the first month of life and focussed on the impact of parity on glucocorticoid sensitivity and adipokine expression in the adipocyte. Twin-bearing sheep of similar body weight and adiposity that consumed identical diets were utilised, and maternal blood samples were taken at 130 days of gestation. One offspring from each twin pair was sampled at 1 day of age, coincident with the time of maximal recruitment of uncoupling protein 1 (UCP1), whilst its sibling was sampled at 1 month, when UCP1 had disappeared. Plasma leptin was lower in nulliparous mothers than in multiparous mothers, and offspring of nulliparous mothers possessed more adipose tissue with increased mRNA abundance of leptin, glucocorticoid receptor and UCP2, adaptations that persisted up to 1 month of age when gene expression for interleukin-6 and adiponectin was also raised. The increase in fat mass associated with firstborn status is therefore accompanied by a resetting of the leptin and glucocorticoid axis within the adipocyte. Our findings emphasise the importance of parity in determining adipose tissue development and that firstborn offspring have an increased capacity for adipogenesis which may be critical in determining later adiposity.

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          Most cited references40

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          Is obesity an inflammatory condition?

          U Das (2015)
          Obesity may be a low-grade systemic inflammatory disease. Overweight and obese children and adults have elevated serum levels of C-reactive protein, interleukin-6, tumor necrosis factor-alpha, and leptin, which are known markers of inflammation and closely associated with cardiovascular risk factors and cardiovascular and non-cardiovascular causes of death. This may explain the increased risk of diabetes, heart disease, and many other chronic diseases in the obese. The complex interaction between several neurotransmitters such as dopamine, serotonin, neuropeptide Y, leptin, acetylcholine, melanin-concentrating hormone, ghrelin, nitric oxide, and cytokines and insulin and insulin receptors in the brain ultimately determines and regulates food intake. Breast-feeding of more than 12 mo is associated with decreased incidence of obesity. Breast milk is a rich source of long-chain polyunsaturated fatty acids (LCPUFAs) and brain is especially rich in these fatty acids. LCPUFAs inhibit the production of proinflammatory cytokines and enhance the number of insulin receptors in various tissues and the actions of insulin and several neurotransmitters. LCPUFAs may enhance the production of bone morphogenetic proteins, which participate in neurogenesis, so these fatty acids might play an important role in brain development and function. It is proposed that obesity is a result of inadequate breast feeding, which results in marginal deficiency of LCPUFAs during the critical stages of brain development. This results in an imbalance in the structure, function, and feedback loops among various neurotransmitters and their receptors, which ultimately leads to a decrease in the number of dopamine and insulin receptors in the brain. Hence, promoting prolonged breast feeding may decrease the prevalence of obesity. Exercise enhances parasympathetic tone, promotes antiinflammation, and augments brain acetylcholine and dopamine levels, events that suppress appetite. Acetylcholine and insulin inhibit the production of proinflammatory cytokines and provide a negative feedback loop for postprandial inhibition of food intake, in part, by regulating leptin action. Statins, peroxisome proliferator-activated receptor-gamma binding agents, non-steroidal antiinflammatory drugs, and infant formulas supplemented with LCPUFAs, and LCPUFAs themselves, which suppress inflammation, may be beneficial in obesity.
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            Size at birth and early childhood growth in relation to maternal smoking, parity and infant breast-feeding: longitudinal birth cohort study and analysis.

            There is remarkably wide variation in rates of infancy growth, however, its regulation is not well understood. We examined the relationship between maternal smoking, parity, and breast- or bottle-feeding to size at birth and childhood growth between 0 and 5 y in a large representative birth cohort. A total of 1,335 normal infants had weight, length/height, and head circumference measured at birth and on up to 10 occasions to 5 y old. Multilevel modeling (MLwiN) was used to analyze longitudinal growth data. Infants of maternal smokers were symmetrically small at birth (p < 0.0005) compared with infants of nonsmokers, however, showed complete catch-up growth over the first 12 mo. In contrast, infants of primiparous pregnancies were thin at birth (p < 0.0005), showed dramatic catch-up growth, and were heavier and taller than infants of nonprimiparous pregnancies from 12 mo onwards. Breast-fed infants were similar in size at birth than bottle-fed infants, but grew more slowly during infancy. Among infants who showed catch-up growth, males caught up more rapidly than females (p = 0.002). In conclusion, early postnatal growth rates are strongly influenced by a drive to compensate for antenatal restraint or enhancement of fetal growth by maternal-uterine factors. The mechanisms that signal catch-up or catch-down growth are unknown but may involve programming of appetite. The importance of nutrition on early childhood growth is emphasized by the marked difference in growth rates between breast- and bottle-fed infants. The sequence of fetal growth restraint and postnatal catch-up growth may predispose to obesity risk in this contemporary population.
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              Weight status in childhood as a predictor of becoming overweight or hypertensive in early adulthood.

              To assess the extent to which weight status in childhood or adolescence predicts becoming overweight or hypertensive by young adulthood. We conducted a prospective study of 314 children, who were 8 to 15 years old at baseline, and were followed up 8 to 12 years later. Weight, height, and blood pressure were measured by trained research staff. Incident overweight was defined as BMI>or=25 kg/m2 among participants who had not been overweight as children. More male subjects (48.3%) than female subjects (23.5%) became overweight or obese between their first childhood visit and the young adult follow-up (p<0.001). Being in the upper one half of the normal weight range (i.e., BMI between the 50th and 84th percentiles for age and gender in childhood) was a good predictor of becoming overweight as a young adult. Compared with children with a BMI<50th percentile, girls and boys between the 50th and 74th percentiles of BMI were approximately 5 times more likely [boys, odds ratio (OR)=5.3, p=0.002; girls, OR=4.8, p=0.07] and those with a BMI between the 75th and 84th percentiles were up to 20 times more likely (boys, OR=4.3, p=0.02; girls, OR=20.2, p=0.001) to become overweight. The incidence of high blood pressure was greater among the male subjects (12.3% vs. 1.9%). Compared with boys who had childhood BMI below the 75th percentile, boys between the 75th and 85th percentiles of BMI as children were four times more likely (OR=3.6) and those at above the 85th percentile were five times more likely (OR=5.1) to become hypertensive. High normal weight status in childhood predicted becoming overweight or obese as an adult. Also, among the boys, elevated BMI in childhood predicted risk of hypertension in young adulthood.

                Author and article information

                Journal
                J Endocrinol
                JOE
                The Journal of Endocrinology
                BioScientifica (Bristol )
                0022-0795
                1479-6805
                February 2010
                24 November 2009
                : 204
                : 2
                : 173-179
                Affiliations
                [1 ]simpleEarly Life Nutrition Research Unit, Academic Child Health, Division of Human Development simpleSchool of Clinical Sciences, University Hospital E Floor East Block, Derby Road, Nottingham, NG7 2UHUK
                [2 ]simpleRespiratory Biomedical Research Unit simpleSchool of Clinical Sciences, University Hospital, University of Nottingham E Floor East Block, Derby Road, Nottingham, NG7 2UHUK
                [3 ]simpleDepartment of Animal Sciences simpleUniversity of Missouri Columbia, Missouri, 65201USA
                Author notes
                (Correspondence should be addressed to M E Symonds; Email: michael.symonds@ 123456nottingham.ac.uk )
                Article
                JOE090358
                10.1677/JOE-09-0358
                2807923
                19934248
                85dcc147-fa30-44f4-82c7-61a021e1d9d4
                © 2010 Society for Endocrinology

                This is an Open Access article distributed under the terms of the Society for Endocrinology's Re-use Licence which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 3 November 2009
                : 24 November 2009
                Funding
                Funded by: European Union Sixth Framework for Research and Technical Development of the European Community – The Early Nutrition Programming Project
                Award ID: FOOD-CT-2005-007036
                Categories
                Regular papers

                Endocrinology & Diabetes
                Endocrinology & Diabetes

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